Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial.

Importance: Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways. Objective: To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index. Design, Setting, and Participants: VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017. Interventions: Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements. Main Outcomes and Measures: For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations. Results: Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI). Conclusions and Relevance: In this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight. Trial Registration: ClinicalTrials.gov Identifier: NCT01169259.

Decreased serum TRAIL is associated with increased mortality in smokers with comorbid emphysema and coronary artery disease.

BACKGROUND: Smokers are highly susceptible to lung and cardiovascular disease that can reduce their survival. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a protein in the circulation that may suppress vascular and pulmonary inflammation. Therefore, we hypothesized that diminished circulating TRAIL levels would be associated with poor survival in smokers with lung and cardiovascular disease. METHODS: Serum TRAIL level was measured by immunoassay in 474 smokers. Coronary atherosclerosis was assessed by coronary artery calcium scoring along with emphysema, lung function, and survival. RESULTS: The 474 smokers were 65.7 ±â€¯6.3 years old and 52.2% male with 55.3 ±â€¯31.5 pack-years of tobacco-exposure. 83 of them died during 3588.2 person-years of follow up. At baseline, lower TRAIL level was associated with more coronary artery calcium (OR = 1.2 per SD, 95%CI 1.1-1.5, p = 0.02), and with history of myocardial infarction (OR = 2.3 per SD, 95%CI 1.2-4.5, p = 0.02), angina (OR = 1.6 per SD, 95%CI 1.1-2.6, p = 0.03), and angioplasty (OR = 1.8 per SD, 95%CI 1.0-3.1, p = 0.04) in models adjusted for cardiovascular risk-factors, FEV1, and emphysema. Also, lower TRAIL level was associated with emphysema severity independent of demographics and tobacco exposure (ß = 0.11 sq. root units, 95% CI 0.01-0.22, p = 0.03). Further, TRAIL level was lowest in smokers with comorbid emphysema and coronary artery calcification rather than either condition alone. Finally, lower TRAIL level was independently associated with increased mortality in smokers particularly in those with comorbid emphysema and coronary artery calcification (HR = 1.38, 95% CI 1.01-1.90). CONCLUSIONS: TRAIL level is reduced in smokers with comorbid emphysema and coronary artery disease, and is associated with reduced survival.

Ideal Cardiovascular Health Metrics in Couples: A Community-Based Study.

BACKGROUND: Determination of the correlation of ideal cardiovascular health variables among spousal or cohabitating partners may guide the development of couple-based interventions to reduce cardiovascular disease risk. METHOD AND RESULTS: We used data from the HeartSCORE (Heart Strategies Concentrating on Risk Evaluation) study. Ideal cardiovascular health, defined by the American Heart Association, comprises nonsmoking, body mass index <25 kg/m2, physical activity at goal, diet consistent with guidelines, untreated total cholesterol <200 mg/dL, untreated blood pressure <120/80 mm Hg, and untreated fasting glucose <100 mg/dL. McNemar test and logistic regression were used to assess concordance patterns in these variables among partners (ie, concordance in achieving ideal factor status, concordance in not achieving ideal factor status, or discordance-only one partner achieving ideal factor status). Overall, there was a low prevalence of ideal cardiovascular health among the 231 couples studied (median age 61 years, 78% white). The highest concordances in achieving ideal factor status were for nonsmoking (26.1%), ideal fruit and vegetable consumption (23.9%), and ideal fasting blood glucose (35.6%). The strongest odds of intracouple concordance were for smoking (odds ratio, 3.6; 95% confidence interval, 1.9-6.5), fruit and vegetable consumption (odds ratio, 4.8; 95% confidence interval, 2.5-9.3) and blood pressure (odds ratio, 3.0; 95% confidence interval, 1.2-7.9). A participant had 3-fold higher odds of attaining ≥3 ideal cardiovascular health variables if he or she had a partner who attained ≥3 components (odds ratio 3.0; 95% confidence interval, 1.6-5.6). CONCLUSIONS: Intracouple concordance of ideal cardiovascular health variables supports the development and testing of couple-based interventions to promote cardiovascular health. Fruit and vegetable consumption and smoking may be particularly good intervention targets.